Dopamine-like effects of cholera toxin in the central nervous system

IT is now well established that cyclic AMP acts as an intracellular "second messenger" in mediating the effects of several hormones on their target cells¹. The hypothesis that cyclic AMP serves a similar function in mediating the effects of certain neurotransmitters in the central nervous system (CNS) has received some support^2,3. For example, the neurotransmitters noradrenaline and dopamine stimulate the synthesis of cyclic AMP in tissue slices or homogenates of brain regions innervated by neurones which use these transmitters^4-6. Further, the actions of these transmitters on neural firing when applied by iontophoresis can be mimicked by cyclic AMP². Bilateral injections of small amounts of dopamine into the nucleus accumbens of rats stimulates locomotor activity⁸. In the present experiments small amounts of cholera toxin were injected bilaterally into the nucleus accumbens of rats and the time course of its effects on adenylate cyclase and locomotor activity were determined. The only known mechanism of action of choleratoxin (choleragen) is activation of adenyl cyclase⁷ in intact cells subsequent to its binding to a cell-surface receptor, the ganglioside GM₁ (refs 9-11). The results support the hypothesis that dopaminergic transmission in the CNS is mediated by cyclic AMP.